Implementing a pharmacist-integrated collaborative model of medication treatment for opioid use disorder in primary care: study design and methodological considerations.

BACKGROUND: Pharmacists remain an underutilized resource in the treatment of opioid use disorder (OUD). Although studies have engaged pharmacists in dispensing medications for OUD (MOUD), few studies have evaluated collaborative care models in which pharmacists are an active, integrated part of a primary care team offering OUD care. METHODS: This study seeks to implement a pharmacist integrated MOUD clinical model (called PrIMO) and evaluate its feasibility, acceptability, and impact across four diverse primary care sites. The Consolidated Framework for Implementation Research is used as an organizing framework for study development and interpretation of findings. Implementation Facilitation is used to support PrIMO adoption. We assess the primary outcome, the feasibility of implementing PrIMO, using the Stages of Implementation Completion (SIC). We evaluate the acceptability and impact of the PrIMO model at the sites using mixed-methods and combine survey and interview data from providers, pharmacists, pharmacy technicians, administrators, and patients receiving MOUD at the primary care sites with patient electronic health record data. We hypothesize that it is feasible to launch delivery of the PrIMO model (reach SIC Stage 6), and that it is acceptable, will positively impact patient outcomes 1 year post model launch (e.g., increased MOUD treatment retention, medication regimen adherence, service utilization for co-morbid conditions, and decreased substance use), and will increase each site's capacity to care for patients with MOUD (e.g., increased number of patients, number of prescribers, and rate of patients per prescriber). DISCUSSION: This study will provide data on a pharmacist-integrated collaborative model of care for the treatment of OUD that may be feasible, acceptable to both site staff and patients and may favorably impact patients' access to MOUD and treatment outcomes. TRIAL REGISTRATION: The study was registered on Clinicaltrials.gov (NCT05310786) on April 5, 2022, https://www. CLINICALTRIALS: gov/study/NCT05310786?id=NCT05310786&rank=1.

Engagement, initiation, and retention in medication treatment for opioid use disorder among young adults: A narrative review of challenges and opportunities.

INTRODUCTION: Opioid Use Disorder (OUD) is a catastrophic public health problem for young adults (YAs) and their families. While medication for OUD (MOUD) is safe, effective, and recognized as the standard of care, its' uptake and success have been limited in YAs compared to older adults. METHODS: This narrative review summarizes the existing literature and highlights select studies regarding barriers to YA MOUD, potential explanations for those barriers, and strategies to overcome them. RESULTS: Barriers are prominent along the entire cascade of care, including: treatment engagement and entry, MOUD initiation, and MOUD retention. Hypothesized explanations for barriers include: developmental vulnerability, inadequate treatment system capacity, stigma against MOUD, among others. Interventions to address barriers include: promotion of family involvement, increasing provider capacity, integration of MOUD into primary care, assertive outreach, and others. CONCLUSIONS: Integrating an adapted version of family coaching from the Community Reinforcement Approach and Family Training (CRAFT) and other models into YA MOUD treatment serves as an example of an emerging novel practice that holds promise for broadening the funnel of engagement in treatment and initiation of MOUD, and enhancing treatment outcomes. This and other developmentally-informed approaches should be evaluated as part of a high-priority clinical and research agenda for improving OUD treatment for YAs.

Implementing Programs to Initiate Buprenorphine for Opioid Use Disorder Treatment in High-Need, Low-Resource Emergency Departments: A Nonrandomized Controlled Trial.

STUDY OBJECTIVE: We hypothesized that implementation facilitation would enable us to rapidly and effectively implement emergency department (ED)-initiated buprenorphine programs in rural and urban settings with high-need, limited resources and dissimilar staffing structures. METHODS: This multicenter implementation study employed implementation facilitation using a participatory action research approach to develop, introduce, and refine site-specific clinical protocols for ED-initiated buprenorphine and referral in 3 EDs not previously initiating buprenorphine. We assessed feasibility, acceptability, and effectiveness by triangulating mixed-methods formative evaluation data (focus groups/interviews and pre/post surveys involving staff, patients, and stakeholders), patients' medical records, and 30-day outcomes from a purposive sample of 40 buprenorphine-receiving patient-participants who met research eligibility criteria (English-speaking, medically stable, locator information, nonprisoners). We estimated the primary implementation outcome (proportion receiving ED-initiated buprenorphine among candidates) and the main secondary outcome (30-day treatment engagement) using Bayesian methods. RESULTS: Within 3 months of initiating the implementation facilitation activities, each site implemented buprenorphine programs. During the 6-month programmatic evaluation, there were 134 ED-buprenorphine candidates among 2,522 encounters involving opioid use. A total of 52 (41.6%) practitioners initiated buprenorphine administration to 112 (85.1%; 95% confidence interval [CI] 79.7% to 90.4%) unique patients. Among 40 enrolled patient-participants, 49.0% (35.6% to 62.5%) were engaged in addiction treatment 30 days later (confirmed); 26 (68.4%) reported attending one or more treatment visits; there was a 4-fold decrease in self-reported overdose events (odds ratio [OR] 4.03; 95% CI 1.27 to 12.75). The ED clinician readiness increased by a median of 5.02 (95% CI: 3.56 to 6.47) from 1.92/10 to 6.95/10 (n(pre)=80, n(post)=83). CONCLUSIONS: The implementation facilitation enabled us to effectively implement ED-based buprenorphine programs across heterogeneous ED settings rapidly, which was associated with promising implementation and exploratory patient-level outcomes.

Technology-Based Interventions in Substance Use Treatment to Promote Health Equity Among People Who Identify as African American/Black, Hispanic/Latinx, and American Indian/Alaskan Native: Protocol for a Scoping Review.

BACKGROUND: Technology-based interventions (TBIs; ie, web-based and mobile interventions) have the potential to promote health equity in substance use treatment (SUTx) for underrepresented groups (people who identify as African American/Black, Hispanic/Latinx, and American Indian/Alaskan Native) by removing barriers and increasing access to culturally relevant effective treatments. However, technologies (emergent and more long-standing) may have unintended consequences that could perpetuate health care disparities among people who identify as a member of one of the underrepresented groups. Health care research, and SUTx research specifically, is infrequently conducted with people who identify with these groups as the main focus. Therefore, an improved understanding of the literature at the intersection of SUTx, TBIs, and underrepresented groups is warranted to avoid exacerbating inequities and to promote health equity. OBJECTIVE: This study aims to explore peer-reviewed literature (January 2000-March 2021) that includes people who identify as a member of one of the underrepresented groups in SUTx research using TBIs. We further seek to explore whether this subset of research is race/ethnicity conscious (does the research consider members of underrepresented groups beyond their inclusion as study participants in the introduction, methods, results, or discussion). METHODS: Five electronic databases (MEDLINE, Scopus, Cochrane Library, CINAHL, and PsycInfo) were searched to identify SUTx research using TBIs, and studies were screened for eligibility at the title/abstract and full-text levels. Studies were included if their sample comprised of people who identify as a member of one of the underrepresented groups at 50% or more when combined. RESULTS: Title/abstract and full-text reviews were completed in 2021. These efforts netted a sample of 185 studies that appear to meet inclusionary criteria. Due to the uniqueness of tobacco relative to other substances in the SUTx space, as well as the large number of studies netted, we plan to separately publish a scoping review on tobacco-focused studies that meet all other criteria. Filtering for tobacco-focused studies (n=31) netted a final full-text sample for a main scoping review of 154 studies. The tobacco-focused scoping review manuscript is expected to be submitted for peer review in Spring 2022. The main scoping review data extraction and data validation to confirm the accuracy and consistency of data extraction across records was completed in March 2022. We expect to publish the main scoping review findings by the end of 2022. CONCLUSIONS: Research is needed to increase our understanding of the range and nature of TBIs being used in SUTx research studies with members of underrepresented groups. The planned scoping review will highlight research at this intersection to promote health equity. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34508.

Perspectives About Emergency Department Care Encounters Among Adults With Opioid Use Disorder.

Importance: Emergency departments (EDs) are increasingly initiating treatment for patients with untreated opioid use disorder (OUD) and linking them to ongoing addiction care. To our knowledge, patient perspectives related to their ED visit have not been characterized and may influence their access to and interest in OUD treatment. Objective: To assess the experiences and perspectives regarding ED-initiated health care and OUD treatment among US patients with untreated OUD seen in the ED. Design, Setting, and Participants: This qualitative study, conducted as part of 2 studies (Project ED Health and ED-CONNECT), included individuals with untreated OUD who were recruited during an ED visit in EDs at 4 urban academic centers, 1 public safety net hospital, and 1 rural critical access hospital in 5 disparate US regions. Focus groups were conducted between June 2018 and January 2019. Main Outcomes and Measures: Data collection and thematic analysis were grounded in the Promoting Action on Research Implementation in Health Services (PARIHS) implementation science framework with evidence (perspectives on ED care), context (ED), and facilitation (what is needed to promote change) elements. Results: A total of 31 individuals (mean [SD] age, 43.4 [11.0] years) participated in 6 focus groups. Twenty participants (64.5%) identified as male and most 13 (41.9%) as White; 17 (54.8%) reported being unemployed. Themes related to evidence included patients' experience of stigma and perceived minimization of their pain and medical problems by ED staff. Themes about context included the ED not being seen as a source of OUD treatment initiation and patient readiness to initiate treatment being multifaceted, time sensitive, and related to internal and external patient factors. Themes related to facilitation of improved care of patients with OUD seen in the ED included a need for on-demand treatment and ED staff training. Conclusions and Relevance: In this qualitative study, patients with OUD reported feeling stigmatized and minimized when accessing care in the ED and identified several opportunities to improve care. The findings suggest that strategies to address stigma, acknowledge and treat pain, and provide ED staff training should be implemented to improve ED care for patients with OUD and enhance access to life-saving treatment.

Implementation facilitation to introduce and support emergency department-initiated buprenorphine for opioid use disorder in high need, low resource settings: protocol for multi-site implementation-feasibility study.

BACKGROUND: For many reasons, the emergency department (ED) is a critical venue to initiate OUD interventions. The prevailing culture of the ED has been that substance use disorders are non-emergent conditions better addressed outside the ED where resources are less constrained. This study, its rapid funding mechanism, and accelerated timeline originated out of the urgent need to learn whether ED-initiated buprenorphine (BUP) with referral for treatment of OUD is generalizable, as well as to develop strategies to facilitate its adoption across a variety of ED settings and under real-world conditions. It both complements and uses methods adapted from Project ED Health (CTN-0069), a Hybrid Type 3 implementation-effectiveness study of using Implementation Facilitation (IF) to integrate ED-initiated BUP and referral programs. METHODS: ED-CONNECT (CTN 0079) was a three-site implementation study exploring the feasibility, acceptability, and impact of introducing ED-initiated BUP in rural and urban settings with high-need, limited resources, and different staffing structures. We used a multi-faceted approach to develop, introduce and iteratively refine site-specific ED clinical protocols and implementation plans for opioid use disorder (OUD) screening, ED-initiated BUP, and referral for treatment. We employed a participatory action research approach and use mixed methods incorporating data derived from abstraction of medical records and administrative data, assessments of recruited ED patient-participants, and both qualitative and quantitative inquiry involving staff from the ED and community, patients, and other stakeholders. DISCUSSION: This study was designed to provide the necessary, time-sensitive understanding of how to identify OUD and initiate treatment with BUP in the EDs previously not providing ED-initiated BUP, in communities in which this intervention is most needed: high need, low resource settings. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03544112) on June 01, 2018: https://clinicaltrials.gov/ct2/show/NCT03544112 .

Patients' perspectives on initiating treatment with extended-release naltrexone (XR-NTX).

BACKGROUND: The National Drug Abuse Treatment Clinical Trials Network (CTN) multisite comparative-effectiveness study ("X:BOT") by Lee et al. (2018) found that, once initiated, extended-release naltrexone (XR-NTX) is as similarly safe and effective as sublingual buprenorphine-naloxone (BUP-NX) for the treatment of opioid use disorder (OUD). However, the detoxification hurdle makes XR-NTX much more difficult to initiate than BUP-NX. This hurdle highlights the need to better understand how patients transition from active opioid use to XR-NTX treatment. OBJECTIVE: To explore patient-identified barriers and facilitators to initiating antagonist treatment (XR-NTX) within the context of an inpatient hospital setting and to reflect postdischarge experiences of those who did and did not initiate XR-NTX treatment. METHOD: We used a convenience sampling strategy to identify study candidates, with the intention of recruiting approximately an equal number of medication-initiated and noninitiated patients. Study participants (N = 14) included 13 males and 1 female with OUD randomized to the XR-NTX arm of the X:BOT study at 1 of the 8 study sites. Seven participants in this sample initiated XR-NTX treatment, and seven did not. Each participant completed one semistructured qualitative interview. We analyzed transcripts using deductive and inductive approaches to conventional content analysis. RESULTS: Although the majority of participants viewed opioid blockade, once-monthly dosing, and no dependence or withdrawal as favorable attributes of XR-NTX, participant ambivalence and lack of familiarity with antagonist treatment were barriers to treatment initiation. The long duration of action and the perceived "commitment" to the medication (e.g., "At the time, a month sounded like a year") compounded the patients' concerns and ambivalence. The majority of those who initiated XR-NTX described it as an effective treatment for OUD, with treatment satisfaction and sustained abstinence emerging as central themes among this population. Some participants who did not successfully initiate XR-NTX expressed regret and a willingness to try XR-NTX in the future. CONCLUSION: Achieving full opioid detoxification is one, but not the only, barrier to initiating treatment with XR-NTX. Additional participant-identified barriers to XR-NTX initiation include fears and ambivalence regarding antagonist treatment. Once initiated, participants perceive XR-NTX to be an effective treatment for maintaining abstinence from opioids. XR-NTX appealed to participants due to the autonomy it affords with once-monthly dosing and no physical dependence.

Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX. METHODS: We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433. FINDINGS: Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group). INTERPRETATION: In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications. FUNDING: NIDA Clinical Trials Network.